Guanidinoacetic Acid (GAA) 'Superior' to Creatine in Terms of Bioenergetic & Health Effects on Brain, Muscle & More?

Not so fast! Just because it may have shuttled more creatine into the muscle GAA does not have to be able to build more strength or size.

It has been a while since the last creatine article was published. Luckily, the publication of the latest paper from Sergej M. Ostojic lab at the University of Novi Sad (Ostojic. 2016b) will change that... as soon as I've analyzed the study and written about it below that is ;-)

First things first, we are dealing with a randomized, double-blind, cross-over trial that was financed by a government grant - not non-existing (as of now) supplement companies who are pimping guanidinoacetic acid (GAA) as a "superior new form of creatine".
Now, technically speaking, this claim would be bogus, anyways, GAA is, after all, an intermediate product formed enzymatically in the liver, pancreas, and kidney in the synthesis of creatine and not "a creatine" - "superior", or not.

The formation of increasing amounts of S-adenosylhomocysteine (SAH) ad subsequently homocysteine (HCY, not shown in the figure, which focuses on the synthesis of creatine) which is potentially bad for your heart- and brain will have to be controlled and means to blunt it will have to be found in future studies (da Silva. 2009).

In the study, of which I want to highlight that the number of subjects limits the significance of its results significantly (consider everything as preliminary evidence), five healthy young men (age 24.3 ± 3.1 years; body mass index 24.9 ± 1.9 kg/m²) volunteered to help the scientists find out, whether 4-week supplementation with 3g / day guanidinoacetic acid (GAA) would be superior to 3.4 g of creatine in facilitating creatine levels and thus have potential performance and health enhancing effects that go beyond those of the 'real thing' (creatine).

Figure 2: Percentage change of tissue creatine levels 0 vs. 4 weeks. GAA denotes guanidinoacetic acid. Values are presented as means, with error bars represent the standard error of the means (SEM). P between trials (Ostojic. 2016b).

As you can see in Figure 2, "GAA (3.0 g/day) resulted in the more powerful rise (up to 16.2%) in tissue creatine levels in vastus medialis muscle, middle cerebellar peduncle, and paracentral gray matter, as compared to creatine" (P < 0.05 | Ostojic 2016).
Ostojic et al. interpret (they didn't test and thus prove that their albeit logical interpretation is adequate) that these results signify that GAA would be "a preferred alternative to creatine for improved bioenergetics in energy-demanding tissue" (my emphasis in Ostojic. 2016). Needless to say that this will require

• Figure 2: Fasting total plasma homocysteine concentration at baseline and at 1, 2, 4, and 6 weeks of supplementation (Week 1, Week 2, Week 4 and Week 6, respectively) in subjects receiving placebo or guanidinoacetic acid (GAA) for 6 weeks at 1.2, 2.4 or 4.8 g/day, respectively (Ostojic. 2014).

  experimental confirmation in studies testing the actual effects on cellular bioenergetics and health effects in energy-demanding tissues such as muscle and brain, 
• further investigations of the potential (health-)relevance of the subsequent increase in methylation reactions that occur during the formation of creatine from GAA in the human body (more specifically, the question "Is the sign. increase in homocysteine levels a health problem for GAA users?" will have to be answered - esp. in the long-term; after all, Ostojic's 2014 study indicated that these start to raise with time / Figure 3), and
• long(er) term studies and studies comparing different dosages of GAA and creatine; after all, the former is supposed to work, because it offers a greater variety of uptake channels - an advantage that may be easy to compensate by (a) administering more creatine (3.4g is not much) and/or for a longer time (4 weeks is short)
• independent confirmation of the experimental results from another lab to exclude a potential bias of the researchers who have been working on the issue for years, now.

References:

• da Silva, Robin P., et al. "Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo." American Journal of Physiology-Endocrinology and Metabolism 296.2 (2009): E256-E261.
• Ganguly, Paul, and Sreyoshi Fatima Alam. "Role of homocysteine in the development of cardiovascular disease." Nutrition journal 14.1 (2015): 1.
• Morris, Martha Savaria. "Homocysteine and Alzheimer's disease." The Lancet Neurology 2.7 (2003): 425-428.
• Ostojic, Sergej M., et al. "Dose–response effects of oral guanidinoacetic acid on serum creatine, homocysteine and B vitamins levels." European journal of nutrition 53.8 (2014): 1637-1643.
• Ostojic, Sergej M., Patrik Drid, and Jelena Ostojic. "Guanidinoacetic acid increases skeletal muscle creatine stores in healthy men." Nutrition 32.6 (2016a): 723-724.
• Ostojic, Sergej M., et al. "Guanidinoacetic acid vs. creatine for improved brain and muscle creatine levels: a superiority pilot trial in healthy men." Applied Physiology, Nutrition, and Metabolism (2016).
• Stead, Lori M., et al. "Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate." American Journal of Physiology-Endocrinology And Metabolism 281.5 (2001): E1095-E1100.